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Effect of Low-Intensity Ultrasound in Regeneration of Articular Cartilage

Effect of Low-Intensity Ultrasound in Regeneration of Articular Cartilage

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Paper que muestra evidencia de la utilidad del ultrasonido terapéutico sobre el cartílago articular
Paper que muestra evidencia de la utilidad del ultrasonido terapéutico sobre el cartílago articular

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Published by: Jorge Campillay Guzmán on Feb 22, 2011
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Reumatol Clin. 2009;
Original Article
Effect of low-intensity pulsed ultrasound on regeneration of joint cartilagein patients with second and third degree osteoarthritis of the knee
Adalberto Loyola Sánchez,
* María Antonieta Ramírez Wakamatzu,
Judith Vázquez Zamudio,
  Julio Casasola,
Claudia Hernández Cuevas,
Amador Ramírez González,
and Jorge Galicia Tapia
Servicio de Medicina de Rehabilitación, CMN 20 de Noviembre, ISSSTE, DF, Mexico
Servicio de Resonancia Magnética, CMN 20 de Noviembre, ISSSTE, DF, Mexico
Servicio de Reumatología, Hospital General de México, SSA, DF, Mexico
Servicio de Radiología e Imagen, Departamento de Resonancia Magnética, CMN 20 de Noviembre ISSSTE, Mexico
Departamento de Investigación, Subdirección General Médica del ISSSTE, DF, Mexico
a r t i c l e
i n f o
 Article history:
Received May 23, 2008Accepted September 9, 2008
Low intensity pulsed ultrasoundKnee osteoarthritisCartilage repair
Palabras clave:
Ultrasonido terapéutico pulsátil de bajaintensidadGonartrosisReparación de cartílago
a b s t r a c t
To determine if the application of low intensity pulsed ultrasound (LIPUS) therapy has apositive effect over the cartilage repair, functional status, and reduction of pain in patients with grade 2 or3 osteoarthrosis of the knee.
This trial was an observational, before and after study without a control group, in which 10 patients(11 knees) were studied. We applied LIPUS therapy with an intensity of 0.3 W/cm
, duty cycle of 50%, givinga total of 36 J/cm
per session during 36 sessions (3 months). The clinical measures were obtained beforethe first session and at the end of the 36th session, and were: cartilage thickness by the analysis of magneticresonance images (MRI) measured by 2 rheumatologists and a radiology specialist, pain by a visual analogscale (1–10 cm) and function/severity by the Lequesne index. We used the non parametric tests of Wilcoxonfor comparing medians and the Spearmans rho for the correlation of the inter observer cartilage thicknessmeasurements defining a
value of <.05 as significant.
We observed an effect on pain (VAS mean before 7.09 [2.54]; mean after 4.18 [2.22];
=.005) andon the function/severity index (Lequesne mean before 10.55 [5.42]; mean after 5 [4.45];
=.008). There waspoor consistency regarding the cartilage thickness measures by resonance imaging between the 3 observers(2 rheumatologists and 1 radiologist) so we were not able to define the presence or absence of effect oncartilage thickness augmentation.
LIPUS has a benefic effect over pain and functionality/severity in patients with Kellgren andLawrence grade 2 and 3 osteoarthritis of the knee. Unfortunately in this study we did not count with areliable measure method to conclude on its effect over cartilage thickness measured by MRI.© 2008 Elsevier España, S.L. All rights reserved.
Efecto del ultrasonido terapéutico pulsátil de baja intensidad sobrela regeneración del cartílago articular en pacientes con gonartrosis de segundo y tercer grado
r e s u m e n
Indagar si la aplicación del ultrasonido terapéutico pulsátil de baja intensidad (USTPBI) producecambios favorables en la regeneración del cartílago articular, así como beneficios clínicos en pacientes quetienen gonartrosis grado 2 o 3 según la clasificación de Kellgren y Lawrence.
Éste es un estudio observacional, tipo antes y después, sin grupo control, en el que se estudiaron10 pacientes (11 rodillas) con gonartrosis grados 2 y 3 (según la clasificación de Kellgren y Lawrence), a losque se les aplicó ultrasonido terapéutico a una intensidad de 0,3 W/cm
pulsátil al 50%, que otorgó un totalde energía de 36 J/cm
por sesión durante 36 sesiones. Las mediciones se realizaron previas al inicio del tra-tamiento y posteriores al término de éste (3 meses después), y consistieron en: grosor del cartílago articularmediante el análisis de imágenes tomadas por resonancia magnética (RM) por 2 reumatólogos y un expertoradiólogo; dolor mediante escala visual analógica (de 1 a 10 cm) y el índice de gravedad de Lequesne.
* Corresponding author.
E-mail address:
betolum54@hotmail.com (A. Loyola Sánchez).1699-258X/$ - see front matter © 2008 Elsevier España, S.L. All rights reserved.
Documento descargado de http://www.reumatologiaclinica.org el 10/12/2009. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.
A. Loyola Sánchez et al / Reumatol Clin. 2009;
 Joint degenerative disease (JDD) is a chronic and degenerativeaffection of all of the joint structures, which starts as damage to thecartilage and progresses though a dynamic adaptation response,leading to irreversible structural change.
 According to the data from the Framingham study, kneeosteoarthritis occurs in at least 33% of persons 60 or older
and isthe main cause of joint inflammation in the United States, with aprevalence of 12%.
 With respect to non-pharmacologic treatment, therapeuticultrasound (TUS) is an important tool, which favors cartilageregeneration.
TUS is based on the emission of mechanical waves of frequenciesover 16
000 Hz, which interact with the bodily tissues and lead tovibrations of an elevated frequency, resulting in either a thermal ora mechanical effect.
In order to achieve the mechanical effect, thesound wave must be applied as a pulse and at a low intensity.In the medical literature there is ample evidence for themechanical effect of low-intensity and pulse ultrasound which favorscell metabolism and the capacity of tissue regeneration.
 Studies in humans have shown a beneficial effect on bone healingin fractures when using this treatment modality,
making theapplication of pulse therapeutic ultrasound (PTUS) useful in tissuessuch as joint cartilage by producing a regenerative effect.On the other hand it is important to mention that TUS in generalis better diffused in liquid environments (with a high water content),such as in the case of the knee.
 Several studies have shown a positive effect of PTUS on theproliferation of stromal cells and chondrocytes, as well as in thedifferentiation of mesenchymal stem cells
; there is also an effecton metabolic stimulation and the formation of extracellular matrix inchondral tissues and an improvement in the histological appearanceof total osteochondral damage in animals.
 Cook et al demonstrated a positive effect of treatment withPTUS on joint cartilage in the repair of osteochondral defectsinduced in the knees of rabbits: they applied a dose of 36 to72 J/cm
daily for 3 months and reported both macroscopic andhistological benefits.
 Until today there are no studies on the effect of PTUS on jointcartilage in patients with knee osteoarthritis. Therefore, the objectiveof this study is to investigate the effect of this treatment modality onthe thickness of the joint cartilage, pain and function of patients withknee osteoarthritis stage 2 and 3 according to the classification of Kellgren and Lawrence.
Material and methods
Observational, before and after study, without a control group.
The study group was composed on 10 patients who belonged tothe Instituto de Seguridad y Servicios Sociales de los Trabajadoresdel Estado (ISSSTE) health system: nine women and 1 man, meanage 67.18 years with an age range of 56 to 81 years of age, with adiagnosis of knee osteoarthritis (according to the criteria of theAmerican College of Rheumatology)
stages 2 and 3 (according tothe classification by Kellgren and Lawrence)
, recruited in the periodbetween March 1, 2007 and May 30, 2007, sent by the departmentsof Rheumatology, Geriatrics, Orthopedics and Physical Rehabilitationof the Centro Médico Nacional (CMN) 20 de Noviembre.The exclusion criteria were to be carriers of an inflammatoryrheumatic disease, having undergone a knee infiltration in the12 weeks prior to the study and to have any formal contraindicationfor the performance of a Magnetic Resonance (MR) imaging study.This study was approved by the Ethics committee of the CMN20 de Noviembre.
Measured using a 10 cm visual analog scale (VAS) (EVA) on2 occasions: 10 cm on 2 occasions: one day before the start of treatmentand one after the application of session number 36 of PTUS.
A severity index of Lequesne
was employed one day before thestart of treatment and one day after session 36 of PTUS. A reductionin 3 points was considered as important clinical improvement, inaccordance to what has been reported in the literature.
Thickness of joint cartilage
Two images were performed (pretreatment and post-treatment)using MR with an Intera set of 1.5 Tesla, 3D/WATSc sequence in acoronal projection, T1 FFE TR 20 TE 10 and Flip 25 technique, obtaining30 coronal slices of 3 mm thickness on the examined knee. Positionof the knees was taken into account (flexion and rotation angles)with the objective of obtaining post-treatment images comparableto the initial ones (using real-time comparisons).Once the images had been obtained, they were printed onphotographic paper but not labeled and taken to 2 independentobservers of the Hospital General de México (J.C. and C.H.C), who didnot know the origin, pretreatment or post-treatment stages of theimages, and to an expert in the interpretation of MR in soft-tissues(Judith Vázquez Zamudio) at the CMN 20 de Noviembre.These observers performed the measurement of joint cartilagethickness in randomly assigned but symmetrical areas in the imagescorresponding to the same patient and on paper using scale measuring
Se utilizaron pruebas estadísticas no paramétricas de Wilcoxon y pruebas de correlación de Spearman, y sedefinió un valor de p < 0,05 como estadísticamente significativo.
Se observó una disminución en la intensidad de dolor (basal media de 7,09
2,54; final mediade 4,18
2,22; p = 0,005) y una mejoría en cuanto a la funcionalidad (basal media de 10,55
5,42; finalmedia de 574,45; p = 0,008) después del tratamiento con USTPBI. Con respecto al grosor medido en la RM,no se obtuvieron mediciones consistentes entre los observadores, por lo que se concluyó que el método demedición no fue reproducible, lo que hizo difícil definir si hubo un incremento o no en el grosor del cartílagoarticular.
El USTPBI tiene un efecto benéfico sobre la disminución del dolor y la mejoría de la funcio-nalidad. Desafortunadamente, en este estudio no se cuenta con un método de medición reproducible paraarrojar una conclusión válida en cuanto al efecto del USTPBI sobre el grosor del cartílago articular© 2008 Elsevier España, S.L. Todos los derechos reservados.
Documento descargado de http://www.reumatologiaclinica.org el 10/12/2009. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.
A. Loyola Sánchez et al / Reumatol Clin. 2009;
(1:20 scale). Regarding the observations of the rheumatologists(J.C. and C.H.C.), they were submitted for agreement testing with aresult under 35%, which led to the decision to perform a new jointmeasurement; final measurements were reached by consensus. Inthe case of measurements performed by an expert, they were carriedout in a single session.The rheumatologist’s measurements and those of the expert werethen submitted to a correlation statistical analysis.
Therapeutic intervention
A Intellect Mobile model Chatanooga therapeutic ultrasoundapparatus was employed, with the following parameters: pulsemode at 50%, intensity 0.3 W/cm
and frequency of 1 MHz, with anenergy output of 36 J/cm
based on the dose used by Cook in a studywith rabbits.
 To calculate the time of application we used the measurementof the tibial plateau area obtained in the initial MR, multiplied itby a factor of 2 to obtain an approximate value of the total area tobe treated and in order to obtain the time needed to deposit theabovementioned energy using the following formula:Time (s):energy (36 J/cm
area to treat (cm
)Potency (0.3 W/cm
7 cm
0.5)Application of PTUS was performed by physical therapy specialistsin the department of Physical Rehabilitation of the CMN (8 in total)and was performed as follows (Figure):– 30° flexed knee (using a cloth in the popliteal area)– PTUS application approach in 2 times (medial and lateralcompartments)– Semifixed head coupling technique (horseshoe)The duration of treatment was 3 months with a frequency of 3 sessions a week and a total of 36 sessions; the total cost of thesewas 7200 Mexican pesos (200 pesos per session).A possible secondary effect of TUS application, due to aphenomenon known as cavitation, consist in the creation of a vacuumbetween the tissues that lead to inflammation and is manifested aspain and edema.
Statistical analysis
Wilcoxon’s test for related variables was employed in order tocompare the earlier variables of pain, severity and thickness inmillimeters with the later ones. In addition, Spearman’s correlationtest was employed for observations performed by rheumatologists(J.C.) and the expert radiologist (J.V.Z.). For this we employed theSPSS version 12 statistical software.
A group of 10 patients (11 knees) was studied, formed by 9 womenand 1 man, with a mean age of 68 years (standard deviation [SD],8.7), a mean weight 72 kg (SD, 9.86), a mean height of 153 cm (SD,6.14) and a body mass index of 30 (SD, 5.8).Within the study group there was a severity (according to theclassification of Kellgren and Lawrence)
of stage 2 in 5 patients(50%) and stage 3 in 5 patients (50%).With respect to the thickness of the cartilage, measured inmillimeters, Spearman correlation test showed an absence of thiswith the exception of the cartilage measured in the medial femoralcompartment in the initial image (
=.011) (Table 1).No significant differences were seen between the baselineand post-treatment cartilage thickness measurements, with theexception of the lateral tibial compartment where a decrease of thiswas seen in the observations performed by the rheumatologists.(
=.028) (Table 2). Joint pain (measured by VAS) showed a significant reduction(initial mean, 7.,09; final mean, 4.18) with a significant
of .005.The Lequesne degree of severity showed a significant reduction(initial mean, 10.55; final mean, 5) with a significant
of .008,interpreted as clinical improvement
(Table 2).
Knee osteoarthritis has an important impact on the quality of lifeand functionality of patients that present it, and there is a tendencytowards an increase in prevalence of this disease explained by theincrease in life expectancy of the general population.To date there are no effective therapeutic interventions proven tohalt the progression or invert the loss of joint cartilage in patientswith knee osteoarthritis. Therefore, pain secondary to this affectionwill continue to impact the quality of life of patients presenting it.The MR technique described in this study is within therecommendations suggested by OMERACT (Outcome Measures inRheumatology Clinical Trials) and OARSI (Osteoarthritis ResearchSociety International) used to define the most useful and reproducibletechniques for the measurement of joint cartilage in the knees.
 Without a doubt, one of the main problems for the evaluation of the different treatments of knee osteoarthritis is how to measure theamount of joint cartilage. Within the available diagnostic tools, MR
Application technique of low-intensity pulse therapeutic ultrasound.
 Table 1
Correlation between cartilage thickness measurements performed by rheumatologist in consensus and the measurements performed by the expertMBFT MCFT LBFT LCFT MBTT MCTT LBTT LCTTSpearman Rho 0.731 0.229 0.248 0.243 0.407 −0.170 −0.086 0.012
.011 .498 .462 .472 .214 .617 .802 .973LBFT indicates lateral baseline femoral thickness; LBTT, lateral baseline tibial thickness; LCFT, lateral control femoral thickness; LCTT, lateral control tibial thickness; MBFT, medialbaseline femoral thickness; MBTT, medial baseline tibial thickness; MCFT, medial control femoral thickness; MCTT, medial control tibial thickness.
Documento descargado de http://www.reumatologiaclinica.org el 10/12/2009. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato.

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